The proposed research is directed toward our understanding of post-translational modification of proteins by protein methylase II (S-adenosylmethionine: protein-carboxyl O-methyltransferase, EC.2.1.1.24) which methyl esterifies free carboxyl groups of the methyl accentor proteins. The enzyme is widely present in nature, both eukaryotes and prokaryotes. The reaction neutralizes anionic charges of the protein substrates forming carboxyl methyl esters. This protein-methyl ester is unstable at physiological conditions and 50% of the ester is hydrolyzed at ph 7 and 37 degrees C. The present research will be focused on the identification of natural endogenous substrate(s) for the enzyme from pituitary glands and erythrocytes. Subsequent alterations of the biological activities of the modified proteins will be studied in conjunction with hormonal potency and erythrocyte membrane function.